Biomarker predicts worsening MS 2 years out, provides treatment window

New research has found that elevation of a biomarker of nerve damage, neurofilament light chain (NfL), predicts the worsening of multiple sclerosis disability up to two years before it occurs. The biomarker provides a timeframe in which interventions can be implemented to prevent or slow worsening disability.

Thought to be an autoimmune disorder in which the immune system eats away at myelin, the nerves’ protective covering, multiple sclerosis (MS) presents with many symptoms, which can be variable and unpredictable. They may be a one-off occurrence or come and go or change in severity over time.

Now, researchers at UCSF have discovered that elevated levels of a biomarker of nerve damage, NfL, can predict worsening MS symptoms up to two years before they occur. It’s the first study to quantify the timeframe preceding disability worsening in the condition.

“The rising of NfL up to two years before signs of disability worsening represents the window when interventions may prevent worsening,” said Ahmed Abdelhak, lead author of the study.

Collaborating with the University of Basel in Switzerland, the researchers looked at the incidence of disability worsening, defined as six months or more of increased impairment reflected in a higher score on the Expanded Disability Status Scale. They distinguished between disability worsening with relapse, which involves residual symptoms or the return of old ones following relapse of MS, and gradual progression of symptoms without relapse.

The researchers tracked data spanning 10 years from two studies which, together, included 1,899 patients. Among those, 570 were identified with MS disability that continued to worsen, of which the majority were independent of relapses.

Elevated NfL levels were associated with up to a 91% higher risk of worsening disability with relapse approximately a year later and up to a 49% higher risk of worsening disability nearly two years later.

“We think that NfL elevation occurs earlier in disability worsening without relapse,” Abdelhak said, suggesting that slow progression of the disease may allow healthcare providers to intervene.

“This aligns with [the] recognition that death of nerve cells is a slow process that builds towards permanent disability and means that interventions to protect nerve cells might have time to also stop disability,” said Ari Green, one of the study’s co-authors.

The findings demonstrate the importance of using NfL as an early marker of nerve damage.

“In addition to the groundbreaking findings on the temporal relationship between NfL increases and gradual disease progression in MS, the study supports the important role of NfL as an early marker of nerve damage,” said Jens Kuhle, another co-author. “Monitoring NfL levels might be able to detect disease activity with higher sensitivity than clinical exam or conventional imaging.”

Further research is needed to examine therapies that might stop the progression of MS during this period of elevated NfL.

The study was published in the journal JAMA Neurology.

Source: UCSF

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